百草枯中毒致大鼠肺损伤病理模型的实验研究

目的:测定百草枯(Paraquat)中毒后大鼠的半数致死量(LD50),并建立一种比较可靠、稳定的肺纤维化动物病理模型。方法:SD大鼠共96只,雌雄各半。50只SD大鼠,雌雄各半,随机分为5组,每组10只,给大鼠一次性腹腔注射不同剂量的百草枯溶液,计算并确定1、2周的半数致死量;确定半数致死量后,另备46只SD大鼠,仍为雌雄各半,其中28只作为中毒组,选取18 mg/kg的剂量一次性腹腔注射给药,18只作为对照组,腹腔注射等体积的无菌等渗盐水,每天观察大鼠中毒症状,并于1、3、5、7、14、21、28、35和42 d分别处死实验组及对照组大鼠,进行肺组织的病理学观察。结果:大鼠腹腔注射百草枯溶液1和2周的半数致死量分别为18.27和17.29mg/kg;95%的可信区间分别为16.61~20.09和15.99~18.67 mg/kg。一次性腹腔注射18 mg/kg剂量的百草枯溶液后,大鼠在不同时间段出现了典型的中毒症状,肉眼及光镜下观察到百草枯中毒致大鼠急性肺损伤及纤维化病理的演变过程。结论:百草枯对大鼠具有很强的毒性,选择适当剂量的百草枯溶液染毒,不仅可减少实验用鼠量降低实验耗材,还可导致大鼠肺出现典型的纤维化。

Experimental study on the pathological rat modelof paraquat-induced acute lung injury and pulmonary fibrosis

Objective:To determine the half lethal dose(LD50) of paraquat in rats and to establish a relatively safe and stable pathological animals model of pulmonary fibrosis.Methods: Ninety-six SD rats totally in half genders.Fifty SD rats in half genders were randomly divided into 5 groups,each had 10 rats.Feed the rats with different doses of liquor of paraquat intraperitoneally one time and definite the half lethal dose of one and two weeks.After that,prepare another forty-six SD rats,also in half genders,as intonication group,twenty-eight rats were treated with the liquor of paraquat in dosage of 18 mg/kg intraperitoneally.As control group,sixteen rats were treated with equivalent volume of normal saline.Observe the toxic symptom daily and rats were sacrificed on day 1,3,5,7,14,21,28,35 and 42 respectively for the histological examination.Results: The half lethal doses of intraperitoneal paraquat of 1 and 2 weeks were 18.27 and 17.29,with 95% confidence intervals of 16.61-20.09 and 15.99-18.67,respectively.After intraperitoneal paraquat injection at the dose of 18 mg/kg,typical toxic symptoms were observed at different times in the rats.The whole process of acute lung injury and fibrosis induced by paraquat intoxication could be seen with the naked eyes or under the light microscope.Conclusion: Paraquat has a strong toxicity to rats.A proper dose of paraquat solution can not only reduce the number of experimental rats,but also induce typical pulmonary fibrosis in rats.